Hardinger K.L.,University of Missouri - Kansas City |
Koch M.J.,Washington University in St. Louis |
Bohl D.J.,Washington University in St. Louis |
Storch G.A.,Virology Laboratory |
Brennan D.C.,Washington University in St. Louis
American Journal of Transplantation | Year: 2010
A 1-year, single-center, randomized trial demonstrated that the calcineurin inhibitor or adjuvant immunosuppression, independently, does not affect BK-viruria or viremia and that monitoring and pre-emptive withdrawal of immunosuppression was associated with resolution of BK-viremia and absence of clinical BK-nephropathy without acute rejection or graft loss. A retrospective 5-year review of this trial was conducted. In cases of BK viremia, the antimetabolite was withdrawn and for sustained viremia, the calcineurin inhibitor was minimized. Five-year follow-up was available on 97% of patients. Overall 5-year patient survival was 91% and graft survival was 84%. There were no differences in patient-survival by immunosuppressive regimen or presence of BK-viremia. Immunosuppression and viremia did not influence graft survival. Acute rejection occurred in 12% by 5-years after transplant, was less common with tacrolimus versus cyclosporine (9% vs. 18%; p = 0.082), and was lowest with the tacrolimus-azathioprine regimen (5%, p = 0.127). Tacrolimus was associated with better renal function at 5-years (eGFR 63 FK vs. 52 CsA mL/min, p = 0.001). Minimization of immunosuppression upon detection of BK-viremia was associated with excellent graft survival at 5-years, low rejection rates and excellent renal function. It is a safe, short and long-term strategy that resulted in freedom from clinically evident BK-virus nephropathy. © 2009 The American Society of Transplantation and the American Society of Transplant Surgeons.
Matthews L.A.,Virology Laboratory |
Lawrance L.M.,University of the West of England |
Gray D.,University of the West of England |
Gray S.,University of the West of England
Epidemiology and Infection | Year: 2011
Rubella, a vaccine-preventable infection. This study examined the antibody status of 11 987 pregnant women during 2005 - 2009. Results showed a non-significant decrease in those with antibody levels of <4·0 IU/ml from 29/2312 (1·3%) in 2005 to 21/2447 (0·9%) in 2009 (Χ 2 for linear trend=0·279, P=0·56) but a significant increase in those with levels of <10 IU/ml from 88/2312 (3·8%) in 2005 to 124/2447 (5·1%) in 2009 (Χ 2 for linear trend=10·27, P=0·001). In women born before 1983 (pre-pubertal vaccination) the proportion of first pregnancies with titres <4 IU was 1·1% (21/2002) compared to 3·4% (69/2022) in those born after 1983 (Χ 2=25·176, P<0·0001) and 2·2% (44/2002) for titres <10 IU compared to 14·0% (282/2022) for those born after 1983 (Χ 2=171·43, P<0·0001). The potential impact of the increase is difficult to determine, requiring further monitoring. This paper discusses the effect of changing immunization programmes on rubella susceptibility in pregnant women. © Copyright Cambridge University Press 2010.
Cheng X.S.,University of Washington |
Bohl D.L.,University of Washington |
Storch G.A.,University of Washington |
Ryschkewitsch C.,U.S. National Institutes of Health |
And 5 more authors.
Journal of the American Society of Nephrology | Year: 2011
BK and JC polyomaviruses can reactivate after transplantation, causing renal dysfunction and graft loss. The incidence of JC reactivation after renal transplant is not well understood. Here, we characterized JC reactivation using samples collected during the first year after transplantation from 200 kidney recipients. We detected BK and JC viruses in the urine of 35 and 16% of transplant recipients, respectively. The median viral load in the urine was 400 times higher for BK virus than JC virus. The presence of BK viruria made concurrent JC viruria less likely: JC viruria was detected in 22% of non-BK viruric recipients compared with 4% of BK viruric recipients (P = 0.001). The codetection rate was 1.5%, which is less than the expected 5.6% if reactivation of each virus was independent (P = 0.001). We did not observe JC viremia, JC nephropathy, or progressive multifocal leukoencephalopathy. The onset of JC viruria was associated with donor, but not recipient, JC-specific antibody in a titer-dependent fashion and inversely associated with donor and recipient BK-specific antibody. Donor and recipient JC seropositivity did not predict BK viruria or viremia. In conclusion, among renal transplant recipients, infection with one polyomavirus inversely associates with infection with the other. Copyright © 2011 by the American Society of Nephrology.
Rottenstreich A.,Unit of Infectious Diseases |
Rottenstreich A.,Technion - Israel Institute of Technology |
Oz Z.K.,Virology Laboratory |
Oren I.,Unit of Infectious Diseases |
Oren I.,Technion - Israel Institute of Technology
Diagnostic Microbiology and Infectious Disease | Year: 2014
Varicella zoster virus (VZV) like other alphaherpes viruses stays latent after its primary infection. During its reactivation, it can infect the central nervous system (CNS) causing a variety of clinical presentations. Using polymerase chain reaction (PCR) for detection of VZV DNA in cerebrospinal fluid (CSF), it is now recognized in some series as the most common causative agent of viral CNS infection. We aimed to investigate in our study the correlation between VZV viral load in the CSF and the clinical course of its infection, using quantitative real-time PCR. For this purpose, we examined 56 specimens of consecutive patients with positive CSF for VZV DNA in a qualitative test, with a clinical picture of meningitis or encephalitis collected over 10. years in Rambam medical center. We found a significant correlation between VZV viral load and the severity and duration of neurological disease. We believe that using quantitative measurement of VZV DNA in the CSF, could serve as a prognostic marker which would influence treatment decisions. © 2014 Elsevier Inc.
Das T.,University of Reunion Island |
Hoarau J.J.,University of Reunion Island |
Bandjee M.C.J.,University of Reunion Island |
Bandjee M.C.J.,Virology Laboratory |
And 2 more authors.
Journal of General Virology | Year: 2015
Chikungunya virus (CHIKV) has recently affected millions of people in the Indian Ocean, with rare cases of encephalopathy and encephalitis occurring in neonates. In the study described herein, the capacity of mouse brain cells to control infection through innate immune antiviral responses was assessed. In vitro, CHIKV principally infected a subpopulation of mouse GFAP+ primary astrocytes. Oligodendrocytes and neurons could also be infected. An innate immune response was engaged by CHIKV-infected astrocytes with elevated expression of mRNAs for IFN-α−β, inflammatory cytokines (e.g. IL-1β, IL-12, IL-10, IL-24) and proapoptotic factors (e.g. TNF-α, FasL, Lymphotoxin B). Programmed cell death through the intrinsic caspase-9 pathway was observed by immunofluorescence in infected astrocytes and neurons but not in oligodendrocytes. Interestingly, microglia did not replicate CHIKV but responded by elevated mitogen-activated protein kinase (MAPK) activity. Intracerebroventricular injection of CHIKV in neonate mice led to the infection of astrocytes. The astrogliosis response was accompanied by a dendritic CD206+ cell mobilization restricted to the site of infection. The results of this study support the paradigm that a multifaceted innate immune response can be mobilized by both professional immune and glial cells to control CHIKV neuroinfection events in neonates. © 2015 The Authors.